La plateforme de pharmacogénomique de précision (PGx) de Leapfrog Bio a mis en évidence un lien cliniquement significatif entre le gène EP300 et les inhibiteurs des protéines à bromodomaine et à domaine extra-terminal (BET)
La présentation décrit la découverte, la caractérisation et le plan de développement clinique de LFB190 de Leapfrog Bio pour le traitement de tumeurs solides associées à la perte de fonction du gène EP300.
San Mateo (Californie), le 10 décembre 2024 (GLOBE NEWSWIRE) — Leapfrog Bio, a clinical-stage precision oncology company identifying novel therapies for undruggable cancer-driving mutations, today announced that Tomas Babak, PhD, the company’s Chief Scientific Officer, will present evidence that Leapfrog Bio’s Precision PGx Platform™ discovered a clinically significant link between the EP300 gene and bromodomain and extra-terminal domain (BET) protein inhibitors. The presentation titled “EP300 loss of function is a pan-cancer sensitizer to BET inhibition” will take place at the AACR Special Conference in Cancer Research in Toronto, Canada, and will focus on the discovery, characterization, and clinical development plan for Leapfrog Bio’s BET inhibitor LFB-190 to treat solid tumors with EP300 loss of function.
Loss of transcriptional control is a hallmark of cancer and can be an essential driver of cancer initiation and progression. BET proteins regulate the expression of multiple cancer-related genes and pathways; several molecules targeting this family of proteins have been tested in early phase clinical trials, although these molecules have shown limited clinical success as monotherapies. After conducting hundreds of pharmacogenetic screens using its Precision PGx Platform™, Leapfrog Bio discovered an interaction between BET protein inhibition and the EP300 gene loss of function (LOF) similar to PARP-BRCA1/HRD in significance. The Company believes it has also discovered the mechanism of action for this synthetically lethal relationship between BET protein inhibition and EP300 LOF.
“It was gratifying to identify this essential interaction, as there has been so much research and activity related to BET inhibitors,” said Tomas Babak, PhD, CSO of Leapfrog Bio. “Discovering a strong interaction between BET proteins and the mutated EP300 gene resulting in LOF—as well as the mechanism that drives it—using the Precision PGx Platform™ is a meaningful validation of the platform’s ability to identify therapies for previously undruggable cancers caused by LOF mutations. Two-thirds of all cancers are caused by mutations in tumor suppressor genes, such as what we see here with EP300, yet less than one percent of LOF tumor suppressor genes have been drugged to date. With Leapfrog Bio’s platform, we can repeatedly uncover candidates that address the unmet needs of patients with cancers caused by LOF mutations.”
Leapfrog’s Lead Candidate, LFB-190, exploits the relationship between BET inhibition and EP300 LOF mutations. The Company’s Phase 2-ready compound was clinically studied prior to Leapfrog’s research, and a recommended Phase 2 dose has been established.
Greg Vontz, CEO of Leapfrog Bio, added, “This discovery demonstrates the ability of the Precision PGx Platform™ to uncover potential therapeutic solutions for the 10M patients with cancers driven by LOF mutations. We have filed IP around this discovery and are currently preparing for LFB-190’s entry into Phase 2 in lung, colon, and bladder cancers in 2025.”
À propos de Leapfrog Bio
Leapfrog Bio est une société d’oncologie de précision au stade clinique qui accélère le développement de médicaments contre le cancer en identifiant des molécules déjà en phase clinique pouvant être repositionnées comme thérapies ciblées pour des cancers associés à des mutations conductrices difficiles à cibler. Son principal programme consiste en un essai de preuve de concept de phase 2 évaluant une petite molécule dans trois cancers solides présentant une mutation génétique avec perte de fonction fréquente, pour laquelle il n’existe actuellement aucune option thérapeutique ciblée. La plateforme de pharmacogénomique de précision (PGx) de Leapfrog Bio constitue un système in vitro reproductible et évolutif permettant d’identifier des médicaments à petites molécules existants pouvant être développés pour traiter des cancers liés à des mutations avec perte de fonction, avec une forte probabilité de succès clinique. Cette plateforme, validée en clinique, est décrite dans l’article évalué par des pairs intitulé « Pharmacogenomic Discovery of Genetically Targeted Cancer Therapies Optimized Against Clinical Outcomes », publié dans la revue npj Precision Oncology (Nature Portfolio). Pour en savoir plus, visitez www.leapfrog.bio.
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Janine McCargo
6 Degrees
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